Hydrochloric Acid → HCID 66731968, compound

HRID 1963425Notes

Reaction equation

HRID 1963425 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([C:15]([OH:17])=O)[CH2:12][CH2:11][N:10]1[C:18]([O:20][CH3:21])=[O:19].N1(C(N2C=CN=C2)=O)C=CN=C1.[CH2:34]([O:36][C:37](=[O:42])[CH2:38]C([O-])=O)[CH3:35].[K+].[Cl-].[Mg+2].[Cl-].Cl>CN1C2C(N=C(N)NC=2NCC1CNC1C=CC(C(NC(C(O)=O)CCC(O)=O)=O)=CC=1)=O.O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([C:15](=[O:17])[CH2:38][C:37]([O:36][CH2:34][CH3:35])=[O:42])[CH2:12][CH2:11][N:10]1[C:18]([O:20][CH3:21])=[O:19]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 66731635HCID 66731635, compound2×

Product 1

HCID 66731968HCID 66731968, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 178479889HCID 178479889, compoundSolvent3×

Procedure

2-(2,4-Dichlorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (2.44 g, 7.35 mmol) (reference compound 23) was dissolved in methyl THF (36.7 mL) and di(1H-imidazol-1-yl)methanone (1.787 g, 11.02 mmol) added. The suspension was stirred at room temperature under nitrogen for 6 h (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (2.250 g, 13.22 mmol) was suspended in methyl THF (36.7 mL) and magnesium chloride (1.259 g, 13.22 mmol) added. The suspension was stirred under nitrogen for 6 h (flask 2). The white suspension in flask 2 was then added to the brown suspension in flask 1. The resulting suspension was stirred at room temperature for 40 h. The mixture was acidified to pH 1 with 3 M HCl. Water and methyl THF were added, the phases separated. The organic layer was washed with water, satd NaHCO3, brine, dried over MgSO4, filtered and evaporated. Purified by flash chromatography using 20% EtOAc in heptane ->50% EtOAc over 10 CV, 3CV at 50%. Repurified by flash chromatography using 20% EtOAc in EtOAc ->30% EtOAc over 12 CV. Methyl 2-(2,4-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.55 g, 52%) was isolated.

Workup

  1. stirringThe suspension was stirred under nitrogen for 6 h (flask 2)
  2. additionThe white suspension in flask 2 was then added to the brown suspension in flask 1
  3. stirringThe resulting suspension was stirred at room temperature for 40 h
  4. customthe phases separated
  5. washThe organic layer was washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customPurified by flash chromatography
  10. customRepurified by flash chromatography

Sources & evidence

ORD record
ord-8c7ced7a3a9c47628b52a54414b7c2b9
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…